Program in Molecular Medicine
Amino Acids, Peptides, and Proteins | Biochemistry | Hemic and Immune Systems | Immunology and Infectious Disease | Molecular Biology | Viruses
The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spatzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well understood. Here, we conducted in vitro assays in the Drosophila S2 cell line with the Toll/interleukin-1 receptor (TIR) homology domains of each Toll family member to determine if they can activate a known target of Toll-1, the promoter of the antifungal peptide gene drosomycin. All TIR family members activated the drosomycin promoter, with Toll-1 and Toll-7 TIRs producing the highest activation. We found that the Toll-1 and Toll-7 ectodomains bind Spz-1, -2, and -5 and also vesicular stomatitis virus (VSV) virions, and that Spz-1, -2, -5, and VSV all activated the promoters of drosomycin and several other AMP genes in S2 cells expressing full-length Toll-1 or Toll-7. In vivo experiments indicated that Toll-1 and Toll-7 mutants could be systemically infected with two bacterial species (Enterococcus faecalis and Pseudomonas aeruginosa), the opportunistic fungal pathogen Candida albicans and VSV with different survival in adult females and males compared with wild-type fly survival. Our results suggest that all Toll family members can activate several AMP genes. Our results further indicate that Toll-1 and Toll-7 bind multiple Spz proteins and also VSV, but differentially affect adult survival after systemic infection, potentially because of sex-specific differences in Toll-1 and Toll-7 expression.
Spätzle, antimicrobial peptide (AMP), cytokine response, gene regulation, insect immunity, sex-specific difference, signal transduction, toll receptor
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© 2019 by The American Society for Biochemistry and Molecular Biology, Inc. Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://www.jbc.org/site/misc/edpolicy.xhtml#copyright.
DOI of Published Version
J Biol Chem. 2019 May 14. pii: jbc.RA118.006804. doi: 10.1074/jbc.RA118.006804. [Epub ahead of print] Link to article on publisher's site
The Journal of biological chemistry
Chowdhury M, Li C, He Z, Lu Y, Liu X, Wang Y, Ip YT, Strand MR, Yu X. (2019). Toll family members bind multiple Spatzle proteins and activate antimicrobial peptide gene expression in Drosophila. Open Access Publications by UMMS Authors. https://doi.org/10.1074/jbc.RA118.006804. Retrieved from https://escholarship.umassmed.edu/oapubs/3850